Biogenic amines may function as neurotransmitters, as modulators of synaptic transmission, and possibly as regulators of synaptic development. The objectives of this research project are to investigate the mechanisms by which the biogenic amine octopamine modulates transmission in both adult and immature neuromuscular synapses of the moth Manduca sexta and to determine if octopamine is necessary for neuro-muscular development. Intracellular recording techniques will be used to determine if octopamine acts directly on the muscle, altering its membrane potential or resistance, and to determine if octopamine alters the frequency and amplitude distribution of miniature excitatory junction potentials. To determine if octopamine acts postsynaptically to modulate the action of the neurotransmitter glutamate, the effect of octopamine on potentials elicited by iontophoretically applied glutamate will be measured. The possibility that octopamine alters the levels of cyclic nucleotides in neuromuscular preparations will be assessed by radioimmunoassay of cyclic AMP and cyclic GMP. The hypothesis that octopamine is necessary for neuro-muscular development will be tested by recording postsynaptic potentials at different stages of development of normal moths and of moths treated with drugs to deplete their octopamine supply. The results wil provide new information about the different susceptibilities of developing and mature neuromuscular synapses to a neuromodulator and about the role of a biogenic amine in synaptic development. The results will also provide a basis for new approaches to diseases characterized by failure of synaptic communication during development or in adults.